scholarly journals Caspase-14 reveals its secrets

2008 ◽  
Vol 180 (3) ◽  
pp. 451-458 ◽  
Author(s):  
Geertrui Denecker ◽  
Petra Ovaere ◽  
Peter Vandenabeele ◽  
Wim Declercq
Keyword(s):  
Current Knowledge ◽  
Keratinocyte Differentiation ◽  
Uvb Radiation ◽  
Epidermal Barrier ◽  
Unique Member ◽  
Evolutionarily Conserved ◽  
Proliferation And Differentiation ◽  
Deficient Mice

Caspase-14 is a unique member of the evolutionarily conserved family of cysteinyl aspartate–specific proteinases, which are mainly involved in inflammation and apoptosis. However, recent evidence also implicates these proteases in proliferation and differentiation. Although most caspases are ubiquitously expressed, caspase-14 expression is confined mainly to cornifying epithelia, such as the skin. Moreover, caspase-14 activation correlates with cornification, indicating that it plays a role in terminal keratinocyte differentiation. The determination of in vitro conditions for caspase-14 activity paved the way to identifying its substrates. The recent development of caspase-14–deficient mice underscored its importance in the correct degradation of (pro)filaggrin and in the formation of the epidermal barrier that protects against dehydration and UVB radiation. Here, we review the current knowledge on caspase-14 in skin homeostasis and disease.

scholarly journals Fucoidan from Undaria pinnatifida Ameliorates Epidermal Barrier Disruption via Keratinocyte Differentiation and CaSR Level Regulation

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 660
Author(s):  
Yu Chen ◽  
Xuenan Li ◽  
Xiaoshuang Gan ◽  
Junmei Qi ◽  
Biao Che ◽  
...  
Keyword(s):  
Undaria Pinnatifida ◽  
Keratinocyte Differentiation ◽  
Mechanistic Study ◽  
Calcium Sensing Receptor ◽  
Epidermal Barrier ◽  
Barrier Disruption ◽  
Calcium Sensing ◽  
External Agents ◽  
Proliferation And Differentiation ◽  
Barrier Repair

The epidermal barrier acts as a line of defense against external agents as well as helps to maintain body homeostasis. The calcium concentration gradient across the epidermal barrier is closely related to the proliferation and differentiation of keratinocytes (KCs), and the regulation of these two processes is the key to the repair of epidermal barrier disruption. In the present study, we found that fucoidan from Undaria pinnatifida (UPF) could promote the repair of epidermal barrier disruption in mice. The mechanistic study demonstrated that UPF could promote HaCaT cell differentiation under low calcium condition by up-regulating the expression of calcium-sensing receptor (CaSR), which could then lead to the activation of the Catenin/PLCγ1 pathway. Further, UPF could increase the expression of CaSR through activate the ERK and p38 pathway. These findings reveal the molecular mechanism of UPF in the repair of the epidermal barrier and provide a basis for the development of UPF into an agent for the repair of epidermal barrier repair.

scholarly journals Comparative study of the stabilities of synthetic in vitro and natural ex vivo transthyretin amyloid fibrils

2020 ◽  
Vol 295 (33) ◽  
pp. 11379-11387 ◽  
Author(s):  
Sara Raimondi ◽  
P. Patrizia Mangione ◽  
Guglielmo Verona ◽  
Diana Canetti ◽  
Paola Nocerino ◽  
...  
Keyword(s):  
Thermodynamic Stability ◽  
Amyloid Fibrils ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Biochemical Properties ◽  
Amyloid Formation ◽  
Free Energies

Systemic amyloidosis caused by extracellular deposition of insoluble fibrils derived from the pathological aggregation of circulating proteins, such as transthyretin, is a severe and usually fatal condition. Elucidation of the molecular pathogenic mechanism of the disease and discovery of effective therapies still represents a challenging medical issue. The in vitro preparation of amyloid fibrils that exhibit structural and biochemical properties closely similar to those of natural fibrils is central to improving our understanding of the biophysical basis of amyloid formation in vivo and may offer an important tool for drug discovery. Here, we compared the morphology and thermodynamic stability of natural transthyretin fibrils with those of fibrils generated in vitro either using the common acidification procedure or primed by limited selective cleavage by plasmin. The free energies for fibril formation were −12.36, −8.10, and −10.61 kcal mol−1, respectively. The fibrils generated via plasmin cleavage were more stable than those prepared at low pH and were thermodynamically and morphologically similar to natural fibrils extracted from human amyloidotic tissue. Determination of thermodynamic stability is an important tool that is complementary to other methods of structural comparison between ex vivo fibrils and fibrils generated in vitro. Our finding that fibrils created via an in vitro amyloidogenic pathway are structurally similar to ex vivo human amyloid fibrils does not necessarily establish that the fibrillogenic pathway is the same for both, but it narrows the current knowledge gap between in vitro models and in vivo pathophysiology.

scholarly journals hiPSC-Derived Epidermal Keratinocytes from Ichthyosis Patients Show Altered Expression of Cornification Markers

2021 ◽  
Vol 22 (4) ◽  
pp. 1785
Author(s):  
Dulce Lima Cunha ◽  
Amanda Oram ◽  
Robert Gruber ◽  
Roswitha Plank ◽  
Arno Lingenhel ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Human Keratinocytes ◽  
In Vitro Models ◽  
Epidermal Keratinocytes ◽  
Altered Expression ◽  
Epidermal Barrier ◽  
Congenital Ichthyosis ◽  
Autosomal Recessive Congenital Ichthyosis ◽  
Induced Pluripotent

Inherited ichthyoses represent a large heterogeneous group of skin disorders characterised by impaired epidermal barrier function and disturbed cornification. Current knowledge about disease mechanisms has been uncovered mainly through the use of mouse models or human skin organotypic models. However, most mouse lines suffer from severe epidermal barrier defects causing neonatal death and human keratinocytes have very limited proliferation ability in vitro. Therefore, the development of disease models based on patient derived human induced pluripotent stem cells (hiPSCs) is highly relevant. For this purpose, we have generated hiPSCs from patients with congenital ichthyosis, either non-syndromic autosomal recessive congenital ichthyosis (ARCI) or the ichthyosis syndrome trichothiodystrophy (TTD). hiPSCs were successfully differentiated into basal keratinocyte-like cells (hiPSC-bKs), with high expression of epidermal keratins. In the presence of higher calcium concentrations, terminal differentiation of hiPSC-bKs was induced and markers KRT1 and IVL expressed. TTD1 hiPSC-bKs showed reduced expression of FLG, SPRR2B and lipoxygenase genes. ARCI hiPSC-bKs showed more severe defects, with downregulation of several cornification genes. The application of hiPSC technology to TTD1 and ARCI demonstrates the successful generation of in vitro models mimicking the disease phenotypes, proving a valuable system both for further molecular investigations and drug development for ichthyosis patients.

scholarly journals miR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions

2020 ◽  
Vol 21 (23) ◽  
pp. 9288
Author(s):  
Lucian Beer ◽  
Polina Kalinina ◽  
Martin Köcher ◽  
Maria Laggner ◽  
Markus Jeitler ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Normal Skin ◽  
Skin Lesions ◽  
Keratinocyte Differentiation ◽  
Psoriatic Skin ◽  
Bioinformatics Analyses ◽  
Epidermal Barrier ◽  
Barrier Formation

The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA–miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1β and INFγ synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.

Effects and Potential Mechanisms of Alcohol Use Disorder on the Fate Determination of Newly Born Neurons in the Hippocampus

2020 ◽  
Vol 55 (6) ◽  
pp. 598-602
Author(s):  
Zahra Shabani ◽  
Mohsen Jafarzadeh Gharehziaaddin
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Mammalian Brain ◽  
Extrinsic Factors ◽  
Proliferation And Differentiation ◽  
Underlying Mechanisms

Abstract In the adult mammalian brain, new functional neurons are generated throughout life because of sustained proliferation and differentiation of neural stem cells (NSCs). The subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus are the two major neurogenic regions in the adult brain. This process is not fixed but is highly modulated by numerous intrinsic and extrinsic factors. Neurogenesis has become in the focus of interest for its involvement in repairing the damaged brain and this motivates researchers to detect controlling mechanisms of this process. Recent evidence suggests that alcohol usage can directly influence adult hippocampal neurogenesis, but its mechanisms remain a matter for debate. Thus, this review summarizes in vivo/in vitro studies on the role of alcohol in hippocampal neurogenesis during adulthood and clarifies its underlying mechanisms by highlighting neurotransmitters and their receptors.

scholarly journals Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth

2003 ◽  
Vol 163 (5) ◽  
pp. 1133-1143 ◽  
Author(s):  
Bénédicte Chazaud ◽  
Corinne Sonnet ◽  
Peggy Lafuste ◽  
Guillaume Bassez ◽  
Anne-Cécile Rimaniol ◽  
...  
Keyword(s):  
Muscle Growth ◽  
Annexin V ◽  
Precursor Cells ◽  
Monocyte Chemoattractant Protein 1 ◽  
Proliferation And Differentiation ◽  
Monocyte Recruitment ◽  
Chemotactic Factors ◽  
Urokinase System

Once escaped from the quiescence niche, precursor cells interact with stromal components that support their survival, proliferation, and differentiation. We examined interplays between human myogenic precursor cells (mpc) and monocyte/macrophages (MP), the main stromal cell type observed at site of muscle regeneration. mpc selectively and specifically attracted monocytes in vitro after their release from quiescence, chemotaxis declining with differentiation. A DNA macroarray–based strategy identified five chemotactic factors accounting for 77% of chemotaxis: MP-derived chemokine, monocyte chemoattractant protein-1, fractalkine, VEGF, and the urokinase system. MP showed lower constitutive chemotactic activity than mpc, but attracted monocytes much strongly than mpc upon cross-stimulation, suggesting mpc-induced and predominantly MP-supported amplification of monocyte recruitment. Determination of [3H]thymidine incorporation, oligosomal DNA levels and annexin-V binding showed that MP stimulate mpc proliferation by soluble factors, and rescue mpc from apoptosis by direct contacts. We conclude that once activated, mpc, which are located close by capillaries, initiate monocyte recruitment and interplay with MP to amplify chemotaxis and enhance muscle growth.

Toll-like receptors and their ligands control mesenchymal stem cell functions

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1422-1432 ◽  
Author(s):  
Meirav Pevsner-Fischer ◽  
Vered Morad ◽  
Michal Cohen-Sfady ◽  
Liat Rousso-Noori ◽  
Alexandra Zanin-Zhorov ◽  
...  
Keyword(s):  
Nuclear Factor ◽  
Toll Like Receptors ◽  
Maintenance And Repair ◽  
Cell Functions ◽  
Proliferation And Differentiation ◽  
Adult Mscs ◽  
Deficient Mice ◽  
Nuclear Factor Κ B ◽  
Msc Differentiation

Abstract Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6 secretion by MSC, induced nuclear factor κ B (NF-κB) translocation, reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC function is the capacity to differentiate into several mesodermal lineages. We show herein that Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic, and chondrogenic cells while sparing their immunosuppressive effect. Our study therefore shows that a TLR ligand can antagonize MSC differentiation triggered by exogenous mediators and consequently maintains the cells in an undifferentiated and proliferating state in vitro. Moreover, MSCs derived from myeloid factor 88 (MyD88)–deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLRs and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC multipotency.

Loss of WNK3 is compensated for by the WNK1/SPAK axis in the kidney of the mouse

2013 ◽  
Vol 304 (9) ◽  
pp. F1198-F1209 ◽  
Author(s):  
Katharina Mederle ◽  
Kerim Mutig ◽  
Alexander Paliege ◽  
Isabel Carota ◽  
Sebastian Bachmann ◽  
...  
Keyword(s):  
Plasma Renin ◽  
Fine Tuning ◽  
Urine Osmolarity ◽  
Water Restriction ◽  
Nacl Transport ◽  
Salt Diet ◽  
Deficient Mice

WNK3 kinase is expressed throughout the nephron and acts as a positive regulator of NKCC2 and NCC in vitro. Here we addressed the in vivo relevance of WNK3 using WNK3-deficient mice. WNK3−/− mice were viable and showed no gross abnormalities. The net tubular function was similar in wild-type (WT) and WNK3−/− mice as assessed by determination of 24-h urine output (1.63 ± .06 in WT and 1.55 ± .1 ml in WNK3−/−, n=16; P=0.42) and ambient urine osmolarity (1,804 ± 62 in WT vs. 1,819 ± 61 mosmol/kg in WNK3−/−, n=40; P=0.86). Water restriction (48 h) increased urine osmolarity similarly in both genotypes to 3,440 ± 220 and 3,200 ± 180 mosmol/kg in WT and WNK3−/− mice, respectively ( n=11; P=0.41). The glomerular filtration rate (343 ± 22 vs. 315 ± 13 ml/min), renal blood flow (1.35 ± 0.1 vs. 1.42 ± 0.04 ml), and plasma renin concentration (94 ± 18 vs. 80 ± 13 ng ANG I·ml−1·h−1) were similar between WT and WNK3−/− mice ( n=13; P=0.54). WNK1 was markedly upregulated in WNK3-deficient mice, whereas the expression of WNK4 was similar in both genotypes. When the mice were fed a salt-restricted diet [0.02% NaCl (wt/wt)] the levels of pSPAK/OSR1, pNKCC2, and pNCC were enhanced in both genotypes compared with the baseline conditions, with the levels in WNK3−/− exceeding those in WT mice. The upregulation of pSPAK/OSR1, pNKCC2, and pNCC in WNK3−/− mice relative to the levels in WT mice when fed a low-salt diet was paralleled by an increased diuresis in response to hydrochlorothiazide. In summary, the overall relevance of WNK3 for the renal reabsorption of NaCl appears to be limited and can be largely compensated for by the activation of WNK3-independent pathways. Consequently, our data suggest that WNK3 may serve as a member of a kinase network that facilitates the fine-tuning of renal transepithelial NaCl transport.

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